p-Toluenesulfonic acid → HCID 136963103, compound

HRID 628397Notes

Reaction equation

HRID 628397 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]([OH:13])=O)[NH:10][C:5]2=[CH:4][CH:3]=1.C[N:15]1[CH2:20]COCC1.O.[NH2:22]N.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]3[O:13][CH:20]=[N:15][N:22]=3)[NH:10][C:5]2=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 79724-MethylmorpholineHCID 24654Hydrazine hydrate (1:1)HCID 116655855-chloro-1H-pyrrolo(3,2-b)pyridine-2-carboxylic acid

Product 1

HCID 136963103HCID 136963103, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To 5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid (2.00 g, 10.2 mmol, from Example 99, Step 1) in THF (40 mL) at 0° C. was added 4-methylmorpholine (1.3 mL, 12 mmol, Aldrich) and isobutyl chloro formate (1.38 mL, 10.7 mmol, Aldrich). After 20 minutes, hydrazine hydrate (3.0 mL, 61 mmol, Aldrich) was added. Cooling was discontinued and the reaction was stirred overnight. The reaction mixture was diluted with EtOAc and washed sequentially with an additional NaHCO3 and brine. The aqueous layer was extracted with EtOAc. Insoluble material at the interface of the layers was collected by filtration. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The product from the extracts and the solid from the filtration were combined and dissolved in trimethylorthoformate (35 mL, Aldrich). p-Toluenesulfonic acid (150 mg, 0.87 mmol, Aldrich) was added and the mixture was heated to 90° C. for 2 hours. Trimethylorthoformate was removed from the filtrate in vacuo to yield a crude product which was used in step 2 without purification.

Workup

  1. temperatureCooling
  2. washwashed sequentially with an additional NaHCO3 and brine
  3. extractionThe aqueous layer was extracted with EtOAc
  4. filtrationInsoluble material at the interface of the layers was collected by filtration
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. filtrationThe product from the extracts and the solid from the filtration
  9. dissolutiondissolved in trimethylorthoformate (35 mL, Aldrich)
  10. customTrimethylorthoformate was removed from the filtrate in vacuo

Sources & evidence

ORD record
ord-df6deff89aa64156b2439ab6ae9d3253
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

Loading…